Sieve or Shield? High Tech Firms and Entrepreneurs and the Impacts of COVID 19 on North American Border Regions

This study examines the role of international borders in the era of the Covid-19 pandemic, which led to unprecedented national decisions to close borders in order to contain the domestic contagion. The idea that borders act as shields conflicts with the needs of cross-border regions, as they rely on networks straddling the borders for goods and services’ provisions. This paper explores different approaches at individual, local, and regional policy levels used to counterbalance such impacts. As evidenced by North American border closures to most non-citizens seeking entry (shield effects), it is important to understand how professionals, firms, and their networks exercised various forms of agency (sieve effects) to negotiate the border and its policies during this most unusual time. Drawing from a comparative study between two North American border regions distinguished for their thriving innovative business ecosystems–Cascadia (Seattle-Vancouver) along the Canada-U.S. border and Calibaja (San Diego-Tijuana) along the Mexico-U.S. border–we seek to understand how COVID-19 measures have influenced cross-border economies through unprecedented responses to crisis management

Cross Border Regional Planning: Insights from Cascadia

This analysis focuses on different levels of Cross-Border Regional Planning (CBRP) processes in the Cascadia borderland. The region is home to the business-led initiative ‘Cascadia Innovation Corridor’ (CIC), designed to foster cross-border economic integration. The CIC strives to build a global innovation ecosystem in Cascadia, including a new high-speed train to connect Seattle and Vancouver. This paper focuses on the scope of the CIC as a CBRP case. The authors evaluate engagement of city governments and coherency between different planning scales to determine whether the CIC has been addressing the major challenges that may prevent tighter economicintegration in Cascadia. The analysis deploys secondary data as well as primary data collected through surveys and interviews. The results shed light on a discrepancy between supra-regional ‘soft planning’ and the urban planning level. The authors offer an evidence-based proposal to broaden the scope of the CIC from a CBRP standpoint

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Sieve or shield : the Canada-U.S. border and high tech labor connectivity within Cascadia under NAFTA and after September 11

This dissertation involves understanding how the particular provisions of Chapter 16 of the North American Free Trade Agreement (NAFTA) dealt with temporary labor mobility of North American professionals across the Canada-U.S. border, with particular emphasis in the Pacific Northwest region (Cascadia) of Canada and the United States. Ideally, NAFTA visa/status provisions should make the temporary entry of professionals easier across the borders of all NAFTA countries - namely Canada, the United States, and Mexico-thus facilitating cross-border trade and enterprise. However, in the case of software engineers, which are a very important category for the expanding high-tech service industries of Vancouver and Seattle, it is arguably not so. Additionally, the concept of 'cross border regions' has gained increasing prominence in policy and academic discourse beginning in the early 1990s. However, in light of September 11, 2001, nation states have found it problematic to balance the need for more open borders to facilitate trade (borders as sieves) with the need for sovereignty or security concerns (borders as shields). Thus, within the context of recent literatures on 'labor mobility/immigration, industrial clusters, borders and borderlands, cross border institutions, and pre/post September 11 security measures', this research aims to better understand the dynamics of transitory immigration of 'knowledge-workers' between Vancouver and Seattle. The research methodology involved in-depth interviews with 10 companies based in Cascadia, 19 officials responsible for creating or interpreting the NAFTA visa provisions, and 15 attorneys primarily in the Cascadia region conversant with facilitating NAFTA and related international work applications. The objectives of this study were to test whether firms' demands for cross-border movements of knowledge workers (e.g. for recruitment or for international sales) were facilitated or impeded by recent NAFTA status provisions, and whether this encumbered the development of a "Cascadia" high-technology cluster, similar to Silicon Valley in the U.S.A. Findings for this dissertation suggest that the mobility of high tech employees working for Vancouver based firms was not impeded by the NAFTA status provisions. However, interpretation of the complex nature of Chapter 16 of NAFTA in part worked against certain occupations emerging in the high-technology field (especially in information technology) and there were significant differences in interpretation by border officials on the Canadian and the United States sides of the international border. Although there were delays and increased anxieties in traveling to the U.S., the events of 9/11 did not stop the flow of Canadian NAFTA professionals into the U.S. and U.S. NAFTA professionals into Canada. While access to the U.S. was not an over-riding problem for Vancouver based firms, many of these firms (and their attorneys) practiced something called "port shopping" when it came to Canadians professionals seeking NAFTA statuses at U.S. ports-of-entry. This involved seeking out a specific port-of-entry along the border line, which - based on the advice of attorneys or other professional colleagues - were felt to be more facilitative towards issuing a NAFTA status without problems. Much of the reputation of each U.S. port-of-entry's attitude towards NAFTA visa provisions was dependent on the interpretation of the port director or other influential personalities within the particular port-of-entry. By comparison, port shopping did not appear so prevalent in the case of U.S. knowledge workers seeking temporary work visa into Canada. This was due to more rigorous on-going standardized training among Canadian border officials, and a deliberate process of communication between front-line port-of-entry officers and headquarters in Ottawa. Since the creation of the U.S. Department of Homeland Security (DHS) in March of 2003, the U.S. had moved more towards the model of Citizenship and Immigration (CIC) Canada in some of its mandate, which requires that all DHS officers be in a state o f "on-going" training. Also, there was a greater demand of professional conduct for DHS officers, which was something that had always been required of CIC officers. As well, all airport U.S. pre-flight inspections port directors now had something called "Discretionary Authority." This power allowed the port director to grant a right of travel into the U.S for a foreigner who, normally, might be denied entry. Canadian port directors have had this power prior to September 11. Additionally, the U.S.'s DHS became more like the Canadian model in its effort to create distance between its port-of-entry officers and immigration attorneys, by not allowing U.S. attorneys to accompany clients through the adjudication process of seeking a NAFTA status at ports-of-entry. (The U.S. government tolerated this activity until August 2003.) Although there was a growing distance between port-of-entry immigration officers and Canadian and U.S. attorneys, firms needed increasingly the help of immigration attorneys with NAFTA applications, especially after September 11. In conclusion, despite the continued mobility o f professionals under NAFTA across the Canada-U.S. border between Vancouver and Seattle, this study indicates that many of the firm's employees were in fact destined for California or other urban centers in the U.S. or the rest of the world, rather than Seattle. The same held true for the one large Seattle based firm interviewed. Much of this firm's movements of NAFTA professionals into Canada were not directed to Vancouver per se. Thus, the study suggests that the economic construct of Cascadia continues to remain a figment in the imagination o f many, and that the cross border-flows of knowledge workers in Vancouver and Seattle reflect "meso/macro regional" and "global" flows rather than "micro regional" flows. Indeed, the patterns of travel for many o f these NAFTA professionals actually fell more closely within the boundaries of David McCloskey's original notion of Cascadia, which was based on an ecological perspective and reached from Alaska into North California; rather than the economic notion of Cascadia constructed by Alan Artibise, which reached from Whistler, B.C. to Eugene, Oregon. Finally, regarding the concept of the Canada-U.S. border being a "Sieve or Shield," there remained a tension between U.S. federal concerns, namely "shield" effects, of heightened security coupled with cross border economic regional needs for more flexible and predictable border management, namely "sieve" effects. This dual mandate of Canada-U.S. border management highlighted the continued bipolar nature that the Canada-U.S. border, as it relates to Chapter 16 of NAFTA, is still embroiled within - continued mandates towards greater North American regional integration (sieve effects) but is still dictated by strong federal policy directives in a post 9/11 climate (shield effects).Arts, Faculty ofGeography, Department ofGraduat